Objective Bismuth‐containing quadruple therapy for Helicobacter pylori (H. pylori) eradication has a relatively high rate of side effects and high cost, thus the option of a high‐dose dual therapy with a high eradication rate and fewer adverse events is a consideration. However, studies of dual therapy are still scarce and are mostly single‐center studies with limited generalizability. Large‐scale, multicenter studies are required. Our study investigated and compared the effectiveness, adverse events, patient compliance, and costs of high‐dose dual therapy with those of bismuth‐containing quadruple therapy in H. pylori‐infected treatment‐naive patients in a prospective, multicenter, open‐label, randomized controlled trial. Method Treatment‐naive patients infected with H. pylori were randomly assigned to receive high‐dose dual therapy (esomeprazole 20 mg 4 times daily and amoxicillin 1000 mg 3 times daily, for 14 days) or bismuth‐containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days). The effectiveness, adverse events, patient compliance, and costs of both groups were compared. Results A total of 700 patients were enrolled. The high‐dose dual therapy group (N = 350) achieved eradication rates of 89.4% (intention‐to‐treat), 90.4% (modified intention‐to‐treat), and 90.6% (per‐protocol), which were similar to rates in the bismuth‐containing quadruple therapy group (N = 350), 84.6%, 88.0%, and 88.2%, respectively (p > 0.05). The high‐dose dual therapy group had a lower rate of adverse events (12.9% vs. 28.1%, p < 0.001) and lower costs (¥590.2 vs. ¥723.22) compared with the quadruple therapy group, respectively. The compliance of both groups was satisfactory (97.7% high‐dose dual vs. 96.8% quadruple, p > 0.05). Conclusion High‐dose dual therapy for H. pylori eradication had similar efficacy and compliance, fewer adverse events, and lower costs than bismuth‐containing quadruple therapy for treatment‐naive patients.
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important target for vaccine and drug development. However, the rapid emergence of variant strains with mutated S proteins has rendered many treatments ineffective. Cleavage of the S protein by host proteases is essential for viral infection. Here, we discovered that the S protein contains two previously unidentified Cathepsin L (CTSL) cleavage sites (CS-1 and CS-2). Both sites are highly conserved among all known SARS-CoV-2 variants. Our structural studies revealed that CTSL cleavage promoted S to adopt receptor-binding domain (RBD) “up” activated conformations, facilitating receptor-binding and membrane fusion. We confirmed that CTSL cleavage is essential during infection of all emerged SARS-CoV-2 variants (including the recently emerged Omicron variant) by pseudovirus (PsV) infection experiment. Furthermore, we found CTSL-specific inhibitors not only blocked infection of PsV/live virus in cells but also reduced live virus infection of ex vivo lung tissues of both human donors and human ACE2-transgenic mice. Finally, we showed that two CTSL-specific inhibitors exhibited excellent In vivo effects to prevent live virus infection in human ACE2-transgenic mice. Our work demonstrated that inhibition of CTSL cleavage of SARS-CoV-2 S protein is a promising approach for the development of future mutation-resistant therapy.
Background. Since December 2019, novel coronavirus- (SARS-CoV-2) infected pneumonia (COVID-19) has rapidly spread throughout China. This study is aimed at describing the characteristics of COVID-19 patients in Wuhan. Methods. 199 COVID-19 patients were admitted to Wuhan Red Cross Hospital in China from January 24th to March 15th. The cases were divided into diabetic and nondiabetic groups according to the history of taking antidiabetic drugs or by plasma fasting blood glucose level at admission, and the difference between groups were compared. Results. Among 199 COVID-19 patients, 76 were diabetic and 123 were nondiabetic. Compared with nondiabetics, patients with diabetes had an older age, high levels of fasting plasma glucose (FPG), D-dimer, white blood cell, blood urea nitrogen (BUN) and total bilirubin (TBIL), lower levels of lymphocyte, albumin and oxygen saturation (SaO2), and higher mortality (P<0.05). The two groups showed no difference in clinical symptoms. Diabetes, higher level of D-dimer at admission, and lymphocyte count less than 0.6×109/L at admission were associated with increasing odds of death. Antidiabetic drugs were associated with decreasing odds of death. Treatment with low molecular weight heparin was not related to odds of death. Conclusion. The mortality rate of COVID-19 patients with diabetes was significantly higher than those without diabetes. Diabetes, higher level of D-dimer, and lymphocyte count less than 0.6×109/L at admission were the risk factors associated with in-hospital death.
Background The efficacy and safety of high‐dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high‐dose dual regimens in treatment‐naive patients of Helicobacter pylori (H. pylori) infection. Materials and Methods The study was a prospective, multicenter, open‐label, randomized controlled trial, including H. pylori‐infected treatment‐naive patients at 12 tertiary hospitals in China. The eligible subjects received high‐dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. Results Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%–91.9%), 84.4% (95% CI 80.0%–88.3%), and 86.7% (95% CI 82.4%–90.2%; p = .315), respectively, based on intention‐to‐treat analysis; 90.3% (95% CI 86.4%–93.3%), 85.5% (95% CI 81.1%–89.2%), and 87.8% (95% CI 83.6%–91.2%; p = .197), respectively, according to modified intention‐to‐treat analysis; and 90.4% (95% CI 86.5%–93.5%), 85.8% (95% CI 81.4%–89.5%), and 88.3% (95% CI 84.1%–91.7%; p = .202) in per‐protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention‐to‐treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. Conclusions Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori‐infected treatment‐naive patients.
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